Glycyrrhizin suppresses the expressions of HMGB1 and ameliorates inflammative effect after acute subarachnoid hemorrhage in rat model.

High-mobility group box 1 (HMGB1), a nuclear protein that has endogenous cytokine-like activity, is involved in early brain injury after subarachnoid hemorrhage (SAH) by mediating inflammatory response. This study was conducted to investigate the effect of glycyrrhizin as an inhibitor of HMGB1 in a rat SAH model. Experimental SAH was induced by using autologous blood injection to prechiasmatic cistern. 15 mg/kg glycyrrhizin was administered immediately after SAH induction, and then administered once at 6, 12 and 18 h. All the rats were sacrificed at 24 h after neurological assessment and frontal brain tissue was taken for assay. Blood-brain barrier (BBB) permeability was determined by Evans blue (EB) extravasation. The expression of HMGB1 were detected by immunofluorescence, western blot and quantitative real-time PCR. Inflammatory mediators (TNF-α, IL-1ß) were measured using specific ELISA. Fluoro-Jade C staining and TUNEL staining was performed for the quantitative assessment of neuronal injury. We found the use of glycyrrhizin significantly improved neurological scores, reduced HMGB1-positive cells, down-regulated mRNA and protein levels of HMGB1, inhibited BBB permeability, and attenuated neuronal cell death and apoptosis after SAH. The up-regulations of inflammation-related molecules (TNF-α, IL-1ß) in SAH rats were suppressed by glycyrrhizin treatment. These findings suggest that glycyrrhizin is a potential candidate for the treatment of inflammatory brain injury after SAH.

Angiotensin-converting enzyme insertion/deletion gene polymorphism and risk of intracranial aneurysm in a Chinese population.

OBJECTIVE: The relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphisms and intracranial aneurysm (IA) has been studied in Caucasian and Japanese populations. The present study aimed to investigate this association in a Chinese population. METHODS: Patients with confirmed IA and age- and sex-matched control subjects without evidence of IA were enrolled. ACE I/D gene polymorphisms were analysed using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: A total of 220 patients with IA and 220 matched controls were enrolled. In the IA group, 64, 106 and 50 patients were of the II, ID and DD genotypes, respectively, compared with 44, 99 and 77 subjects in the control group. The ACE DD genotype and D allele frequencies were significantly lower in the IA group compared with the control group. There were no statistically significant differences in the site, shape, size and Fisher Grade of aneurysms between genotypes in patients with IA. CONCLUSION: The ACE DD genotype may be a protective factor for IA in a Chinese population.